The proposed research projects are designed to elucidate the relationship of acute and chronic ethanol ingestion on the lipid peroxidation process of liver, one of the most vulnerable organs to injury from ethanol abuse. The ability of the antioxidants to prevent the induction of ethanol-induced hepatic injury, as well as other forms of chemical induced liver injury when administered prophylactically has been amply demonstrated. The therapeutic use of antioxidants in ethanol and other forms of chemical induced liver injury will be evaluated in further consideration of possible future clinical employment of antioxidants. The mechanism by which antioxidants profoundly modify hepatic injury will be investigated. Since our previous studies suggested that ethanol must be metabolized before fatty liver develops, as denoted by the use of pyrazole, extensive studies will be made on the mechanism by which pyrazole inhibits the development of ethanol-induced hepatic injury. Studies with disulfarim will also be conducted. The influence of antioxidants on other types of chemical induced hepatic injury such as allyl alcohol, allyl formate and hydrazine will be studied in a further attempt to define the possible importance of lipid peroxidation as a factor in hepatic cell injury. These composite studies will permit a delineation of the molecular mechanisms of various facets of ethanol-induced hepatic injury as well as the further evaluation of possible resolution of alcohol as well as other types of chemical induced hepatic cell injury by employment of antioxidants.